The Potential Role of Growth Hormone on the Endometrium in Assisted Reproductive Technology

Liu, Fen-Ting; Wu, Ze; Yan, Jie; Norman, Robert J.; Li, Rong

doi:10.3389/fendo.2020.00049

Cited by 16 publications

(19 citation statements)

References 58 publications

(80 reference statements)

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“…The mechanisms underlying the effects of GH on endometrial thickness and uterine perfusion remain unclear. Animal models and in vitro cell cultures have been used to address this question, from basic science to the development and assessment of GH in clinical application ( 114 ). Targeted depletion of Ghr in mice leads to a detrimental impact on reproduction during early pregnancy because of fewer uterine implantation sites ( 115 ).…”

Section: Growth Hormone and Human Uterine Receptivitymentioning

confidence: 99%

Growth hormone in fertility and infertility: Mechanisms of action and clinical applications

et al. 2022

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Secreted by the anterior pituitary gland, growth hormone (GH) is a peptide that plays a critical role in regulating cell growth, development, and metabolism in multiple targeted tissues. Studies have shown that GH and its functional receptor are also expressed in the female reproductive system, including the ovaries and uterus. The experimental data suggest putative roles for GH and insulin-like growth factor 1 (IGF-1, induced by GH activity) signaling in the direct control of multiple reproductive functions, including activation of primordial follicles, folliculogenesis, ovarian steroidogenesis, oocyte maturation, and embryo implantation. In addition, GH enhances granulosa cell responsiveness to gonadotropin by upregulating the expression of gonadotropin receptors (follicle-stimulating hormone receptor and luteinizing hormone receptor), indicating crosstalk between this ovarian regulator and the endocrine signaling system. Notably, natural gene mutation of GH and the age-related decline in GH levels may have a detrimental effect on female reproductive function, leading to several reproductive pathologies, such as diminished ovarian reserve, poor ovarian response during assisted reproductive technology (ART), and implantation failure. Association studies using clinical samples showed that mature GH peptide is present in human follicular fluid, and the concentration of GH in this fluid is positively correlated with oocyte quality and the subsequent embryo morphology and cleavage rate. Furthermore, the results obtained from animal experiments and human samples indicate that supplementation with GH in the in vitro culture system increases steroid hormone production, prevents cell apoptosis, and enhances oocyte maturation and embryo quality. The uterine endometrium is another GH target site, as GH promotes endometrial receptivity and pregnancy by facilitating the implantation process, and the targeted depletion of GH receptors in mice results in fewer uterine implantation sites. Although still controversial, the administration of GH during ovarian stimulation alleviates age-related decreases in ART efficiency, including the number of oocytes retrieved, fertilization rate, embryo quality, implantation rate, pregnancy rate, and live birth rate, especially in patients with poor ovarian response and recurrent implantation failure.

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Section: Growth Hormone and Human Uterine Receptivitymentioning

confidence: 99%

Growth hormone in fertility and infertility: Mechanisms of action and clinical applications

et al. 2022

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“…A large majority of studies in the medical literature supplemented patients with GH, however, only during stimulation or, at best, starting about 2 weeks before stimulation start. Such supplementation, like androgen supplementation which supports follicle growth with identical timing [21], will not result in desired effects on granulosa cells of growing follicles (and, therefore, oocytes), though they may, at right concentrations, exert beneficial endometrial effects [35,36]. Second, the literature also varies greatly in daily dosages of GH that were administered.…”

Section: Limitations Summary and Conclusionmentioning

confidence: 99%

Importance of IGF-I levels in IVF: potential relevance for growth hormone (GH) supplementation

Gleicher

Darmon

Molinari

et al. 2022

J Assist Reprod Genet

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Purpose Growth hormone (GH) supplementation in association with in vitro fertilization (IVF) is worldwide again increasing, even though study outcomes have been discrepant. Since GH acts via insulin-like growth factor-1 (IGF-1), its utilization in IVF would only seem to make sense with low IGF-1. We, therefore, determined whether IGF-I levels affect IVF outcomes. Methods Retrospectively, 302 consecutive first fresh, non-donor IVF cycles were studied, excluding patients on GH supplementation. Patients were divided into 3 subgroups: IGF-1 in lower 25th percentile (group A, < 132 ng/mL, n = 64); 25th–75th percentile (B, 133–202 ng/mL, n = 164), and upper 25th percentile (C, > 202 ng/mL, n = 74). IGF-1 was tested immunochemiluminometric with normal range at 78–270 ng/mL. Because of the study patients’ adverse selection and low pregnancy chances, the main outcome measure for the study was cycle cancellation. Secondary outcomes were oocyte numbers, embryos transferred, pregnancies, and live births. Results Group A was significantly older than B and C (P = 0.019). IGF-1 decreased with increasing age per year by 2.2 ± 0.65 ng/mL (P = 0.0007). FSH was best in group B and worst in A (trend, P = 0.085); AMH was best in B and worst in A (N.S.). Cycle cancellations were lowest in C (11.6%) and highest in A (25.0%; P = 0.042). This significance further improved with age adjustment (P = 0.021). Oocytes, embryo numbers, pregnancies, and live birth rates did not differ, though oocyte numbers trended highest in B. Conclusions Here presented results support the hypothesis that IGF-1 levels affect IVF outcomes. GH treatments, therefore, may be effective only with low IGF-1.

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“…Studies in recent years have shown that growth hormone can improve ovarian responsiveness, promote endometrial growth, improve ovulation treatment in patients with low ovarian response, and increase pregnancy rates with cyclic ovulation. However, the use of growth hormone in the promotion of ovulation in patients with ROS warrants further investigation (89)(90)(91)(92). Mueller et al (63) reported a case of ROS in which follicle growth was not successfully induced with growth hormone.…”

Section: Growth Hormone Combined With Ovulation Inductionmentioning

confidence: 99%

Resistant ovary syndrome: Pathogenesis and management strategies

Shen

Lei

2022

Front. Med.

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Resistant ovary syndrome (ROS) is a rare and difficult gynecological endocrine disorder that poses a serious risk to women’s reproductive health. The clinical features are normal sex characteristics, regular female karyotype, and usual ovarian reserve, but elevated endogenous gonadotropin levels and low estrogen levels with primary or secondary amenorrhea. Although there have been many case reports of the disease over the past 50 years, the pathogenesis of the disease is still poorly understood, and there are still no effective clinical management strategies. In this review, we have collected all the current reports on ROS and summarized the pathogenesis and treatment strategies for this disease, intending to provide some clinical references for the management and treatment of this group of patients and provide the foothold for future studies.

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The Potential Role of Growth Hormone on the Endometrium in Assisted Reproductive Technology

Cited by 16 publications

References 58 publications

Growth hormone in fertility and infertility: Mechanisms of action and clinical applications

Growth hormone in fertility and infertility: Mechanisms of action and clinical applications

Importance of IGF-I levels in IVF: potential relevance for growth hormone (GH) supplementation

Resistant ovary syndrome: Pathogenesis and management strategies

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